Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection

Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

Intramacrophage survival of uropathogenic Escherichia coli : differences between diverse clinical isolates and between mouse and human macrophages

Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24 h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24 h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1+ vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival.

Escherichia coli 83972 expressing a P fimbriae oligosaccharide receptor mimic impairs adhesion of Uropathogenic E. coli

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are a significant health concern, exacerbated by the rapid emergence of multidrug resistant strains refractory to antibiotic treatment. P fimbriae are strongly associated with upper urinary tract colonization due to specific binding to α-D-galactopyranosyl-(1-4)-β-D-galactopyranoside receptors in the kidneys. Thus, inhibiting P-fimbrial adhesion may reduce the incidence of UPEC-mediated UTI. E. coli 83972 is an asymptomatic bacteriuria isolate successfully used as a prophylactic agent to prevent UTI in human studies. We constructed a recombinant E. coli 83972 strain displaying a surface-located oligosaccharide P fimbriae receptor mimic that bound to P-fimbriated E. coli producing any of the 3 PapG adhesin variants. The recombinant strain, E. coli 83972:: lgtCE, impaired P fimbriae–mediated adhesion to human erythrocytes and kidney epithelial cells. Additionally, E. coli 83972::lgtCE impaired urine colonization by UPEC in a mouse UTI model, demonstrating its potential as a prophylactic agent to prevent UTI.

The relationship between ambient ultraviolet radiation (UVR) and objectively measured personal UVR exposure dose is modified by season and latitude

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3 °S), Brisbane (27.5 °S), Canberra (35.3 °S) and Hobart (42.8 °S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median=1.1, IQR: 0.5–2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r=0.23, p<0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r=0.50) and at high latitudes (Hobart, r=0.50; Canberra, r=0.39), to null or even slightly negative correlations, in summer (r=0.01) and at low latitudes (Townsville, r=-0.06; Brisbane, r=-0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances.

Author response to : Brough et al. in response to the recently published article : Lottering,N., MacGregor,D.M.,Barry,M.D.,Reynolds,M.S., Gregory,L.S., 2014. Introducing standardized protocols for anthropological measurement of virtual sub-adult crania using computed tomography 2(1),34–38

Firstly, we would like to thank Ms. Alison Brough and her colleagues for their positive commentary on our published work [1] and their appraisal of our utility of the “off-set plane” protocol for anthropometric analysis. The standardized protocols described in our manuscript have wide applications, ranging from forensic anthropology and paleodemographic research to clinical settings such as paediatric practice and orthopaedic surgical design. We affirm that the use of geometrically based reference tools commonly found in computer aided design (CAD) programs such as Geomagic Design X® are imperative for more automated and precise measurement protocols for quantitative skeletal analysis. Therefore we stand by our recommendation of the use of software such as Amira and Geomagic Design X® in the contexts described in our manuscript...

Becoming a pharmacist : students' perceptions of their curricular experience and professional identity formation

Introduction Student professional identity formation is important for enabling the successful transition between academic education and professional practice. Recognition of this has resulted in significant changes in professional education (e.g., the inclusion of experiential placements and authentic learning experiences). There is limited research that examines how the curricular experience influences pharmacy studentsʼ professional identity formation. Methods Using focus groups, comprising 82 students from all levels of a four-year Australian undergraduate pharmacy course, this study examined studentsʼ perceptions of their overall curricular experience and examined how these experiences influenced the construction of their professional identities. Results Our analysis found that the pharmacy students struggled with their professional identity formation. Many were entering the degree with little understanding of what being a pharmacist entailed. Once in the educational context, the nature of the role became both apparent and idealistic but not enacted. Students experienced dissonance between the idealistic notion of pharmacy practice and the realities of placements, and this may have been enhanced by a lack of patient-centered care role models. This struggle left them concluding that the role of the pharmacist was constrained and limited. Conclusions We argue that professional identity formation needs to be in the foreground from commencement of the degree and throughout the curriculum.

Pharmacy educators' intention for the curriculum : an Australian pilot study

Background: Pharmacy educators play an important role in supporting the professional identity formation of students, particularly in relation to their perceptions and strategies for the curriculum and subsequent learning experiences. Aim: To explore pharmacy educators’ perceptions of the purpose of the pharmacy curriculum and how they contribute to students’ development as pharmacists. Methods: A one-off survey using a 20-item questionnaire distributed to all pharmacy educators at a single school of pharmacy who contributed to an Australian undergraduate pharmacy degree program. Results: Most educators viewed the curriculum and their role from a traditional perspective. The educators felt the key purpose of the curriculum was to develop competent pharmacists by providing students with knowledge and skills. There was a limited emphasis on patient-centredness. Conclusion: Whilst educators were focused on developing competent pharmacists through the provision of knowledge and skills, important learning opportunities supporting identity formation may be missed.

Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4-treated mice

Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, and liver failure. Embryonic and mesenchymal stem cells have been shown to reduce experimental liver fibrosis but have potential limitations, including the formation of dysplastic precursors, tumors, and profibrogenic cells. Other stem-like cells may reduce hepatic inflammation and fibrosis without tumor and profibrogenic cell formation. To test this hypothesis we transplanted human amnion epithelial cells (hAEC), isolated from term delivered placenta, into immunocompetent C57/BL6 mice at week 2 of a 4-week regimen of carbon tetrachloride (CCl4) exposure to induce liver fibrosis. Two weeks following hAEC infusion, intact cells expressing the human-specific markers inner mitochondrial membrane protein and human leukocyte antigen-G were found in mouse liver without evidence of host rejection of the transplanted cells. Human albumin, known to be produced by hAEC, was detected in sera of hAEC-treated mice. Human DNA was detected in mouse liver and also spleen, lungs, and heart of some animals. Following hAEC transplantation, CCl4-treated animals showed decreased serum ALT levels and reduced hepatocyte apoptosis, compared to controls. hAEC-treated mouse liver had lower TNF-α and IL-6 protein levels and higher IL-10 compared to animals given CCl4 alone. Compared to CCl4 controls, hAEC-treated mice showed fewer activated collagen-producing hepatic stellate cells and less fibrosis area and collagen content. Reduced hepatic TGF-β levels in conjunction with a twofold increase in the active form of the collagen-degrading enzyme matrix metalloproteinase-2 in hAEC-treated mice compared to CCl4 controls may account for the reduction in fibrosis. hAEC transplantation into immunocompetent mice leads to cell engraftment, reduced hepatocyte apoptosis, and decreased hepatic inflammation and fibrosis.

Addressing factory needs in cane variety selection

Cane fibre content has increased over the past ten years. Some of that increase can be attributed to new varieties selected for release. This paper reviews the existing methods for quantifying the fibre characteristics of a variety, including fibre content and fibre quality measurements – shear strength, impact resistance and short fibre content. The variety selection process is presented and it is reported that fibre content has zero weighting in the current selection index. An updated variety selection approach is proposed, potentially replacing the existing selection process relating to fibre. This alternative approach involves the use of a more complex mill area level model that accounts for harvesting, transport and processing equipment, taking into account capacity, efficiency and operational impacts, along with the end use for the bagasse. The approach will ultimately determine a net economic value for the variety. The methodology lends itself to a determination of the fibre properties that have a significant impact on the economic value so that variety tests can better target the critical properties. A low-pressure compression test is proposed as a good test to provide an assessment of the impact of a variety on milling capacity. NIR methodology is proposed as a technology to lead to a more rapid assessment of fibre properties, and hence the opportunity to more comprehensively test for fibre impacts at an earlier stage of variety development.

Better half-dead than read? The Mezzomorto cases and their implications for literary culture in the 1930s

This article focusses on the two libel cases arising from Brian Penton's review of Vivian Crockett's novel Mezzomorto for the Bulletin in 1934, viewing them as points of entry into Australian literary politics in the 1930s, and as windows on to one of the most enduring and interesting feuds in Australian literary culture, that between P.R. 'Inky' Stephensen, self-styled 'Bunyip Critic,' and Brian Penton, arch exponent of 'destructive criticism' and scourge of parochial pretension. The cases are particularly interesting for what they reveal about the evolving positions of two influential figures in Australian writing of the 1930s and 1940s. They also play in to contemporary debates about the state and status of 'literature' in Australia. And while Penton's biographer Patrick Buckridge avers that the cases did not impact on any of the larger contemporary literary issues (meaning censorship and free speech), a case may be made for the significance of the libel actions in the context of attempts to establish an industrial and cultural presence for a diverse range of Australian writing.

Commercial friendships between gay salesmen and straight female customers

Perhaps it is now sacrosanct in marketing to contemplate that many service encounters, especially those in retail settings, are social encounters in which bonds between and among customers and employees are critical drivers of consumption (Beatty et al., 1996; Rosenbaum, 2006). Indeed, within retail settings, it is often possible for salespeople and customers to form so-called “commercial friendships” (Price and Arnould, 1999). These friendships result in both salespeople and their customers having social interactions that are close to those experienced in personal friendships (Swan et al., 2001), and which are extremely satisfying for all parties. Outside of marketing, the social science literature (Grigoriou, 2004; Rumens, 2008; Russell, DelPriore, Butterfield, and Hill, 2013) and popular press (de la Cruz and Dolby, 2007; Hopcke and Rafaty, 1999; Tilmann-Healy, 2001, Whitney, 1990) is replete with knowledge regarding the “absolutely fabulous” friendships (Hopcke and Rafaty, 1999) that often form between gay men and straight women. In fact, Western culture regularly highlights the compatibility of gay men and straight women in film, television, and writing, to the extent that they have now influenced popular thinking on the topic, so that gay men and straight females are viewed as sharing common plights and interests (Rumens, 2008). Yet, thus far, marketing researchers have looked askance at the effect of friendships between gay male employees and heterosexual female customers in consumption settings, such as retail stores and boutiques. Indeed, with the exception of Peretz’s (1995) participant observation regarding how young and outwardly gay salesmen use their ambiguous gender to sell women’s clothing, in a Paris-based luxury boutique, any theoretical explorations regarding retail-based commercial friendships between gay salesmen and female customers are non-existent—until now. This research addresses this apparent chasm in the literature by putting forth an original framework that shows how the emotional closeness between gay salesmen and female customers, due to the absence of sexual interest and inter-female competition, results in an intense emotional closeness, that facilitates pleasurable retail transactions, customer satisfaction, loyalty, and positive word-of-mouth. In doing so, this work extends the commercial friendship paradigm by considering retail-based, commercial friendships between an under-researched marketplace dyad; gay men and straight females. It is worth noting here that some straight women may find the idea of commercial friendships with gay salesmen as undesirable, due to the very notion of having relationships with retail organizations or employees (Noble and Phillips, 2004), or a personal disdain for homosexuality.

Inquiry into Suicide in Australia (Submission)

This submission is informed by an ongoing Australian Research Council (ARC) Discovery Project: “Safeguarding Rural Australia: Addressing Masculinity and Violence in Rural Settings”. Due to project status, presentation of emergent findings, although relevant to this inquiry, would be premature and could jeopardise extant reporting and publishing obligations. Accordingly, our comments are restricted and are essentially with respect to Terms of Reference (c) dealing with the accuracy of suicide reporting in Australia.

Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer

Objectives: Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues. Methods: Women treated for endometrial cancer (n = 1243) were followed-up 3–5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates. Results: Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was > 50% for women with 15 + nodes removed and 2–3 additional risk factors, 30–41% for those with 15 + nodes removed plus 0–1 risk factors or 6–14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1–5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain. Conclusion: Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support.

Can skin cancer prevention and early detection be improved via mobile phone text messaging? a randomised, attention-control trial.

Objective. To test the impact of a theory-based, SMS (text message)-delivered behavioural intervention (Healthy Text) targeting sun protection or skin self-examination behaviours compared to attention-control. Method. Overall, 546 participants aged 18–42 years were randomised using a computer-generated number list to the skin self-examination (N = 176), sun protection (N = 187), or attention-control (N = 183) text messages group. Each group received 21 text messages about their assigned topic over 12 months (12 weekly messages for three months, then monthly messages for the next nine months). Data was collected via telephone survey at baseline, three-, and 12-months across Queensland from January 2012 to August 2013. Results. One year after baseline, the sun protection (mean change 0.12; P = 0.030) and skin self-examination groups (mean change 0.12; P = 0.035) had significantly greater improvement in their sun protection habits (SPH) index compared to the attention-control group (reference mean change 0.02). The increase in the proportion of participants who reported any skin self-examination from baseline to 12 months was significantly greater in the skin self-examination intervention group (103/163; 63%; P < 0.001) than the sun protection (83/173; 48%), or attention-control (65/165; 36%) groups. There was no significant effect of the intervention for participants who self-reported whole-body skin self-examination, sun tanning behaviour, or sunburn behaviours. Conclusion. The Healthy Text intervention was effective in inducing significant improvements in sun protection and any type of skin self-examination behaviours.

Enhancing Raman signal sufficiently for practical sensing applications

Techniques are presented for enhancing weak Raman scattering signals for rapid yet accurate substance detection. Novel surfaces that allow signal enhancement quantification are described as are eye-safe methodologies that maximize the stand-off Raman detection range.